OBJECTIVES: This study sought to determine whether post-operative neurocognitive dysfunction (POCD) occurs after ablation for atrial fibrillation (AF). BACKGROUND: Ablation for AF is a highly effective strategy; however, the risk of transient ischemic attack and stroke is approximately 0.5% to 1%. In addition, magnetic resonance imaging studies report a 7% to 14% prevalence of silent cerebral infarction. Whether cerebral ischemia results in POCD after ablation for AF is not well established. METHODS: The study included 150 patients; 60 patients undergoing ablation for paroxysmal atrial fibrillation (PAF), 30 patients undergoing ablation for persistent atrial fibrillation (PeAF), and 30 patients undergoing ablation for supraventricular tachycardia (SVT) were compared with a matched nonoperative control group of patients with AF awaiting radiofrequency ablation (n = 30). Eight neuropsychological tests were administered at baseline and at 2 days and 90 days post-operatively. The tests were administered at the same time points to the nonoperative control group. The reliable change index was used to calculate POCD. RESULTS: The prevalences of POCD at day 2 post-procedure were 28% in patients with PAF, 27% in patients with PeAF, 13% in patients with SVT, and 0% in control patients with AF (p = 0.007). At day 90, the prevalences of POCD were 13% in patients with PAF, 20% in patients with PeAF, 3% in patients with SVT, and 0% in control patients with AF (p = 0.03). When analyzing the 3 procedural groups together, 29 of 120 patients (24%) manifested POCD at day 2 and 15 of 120 patients (13%) at day 90 post-procedure (p = 0.029). On univariate analysis, increasing left atrial access time was associated with POCD at day 2 (p = 0.04) and day 90 (p = 0.03). CONCLUSIONS: Ablation for AF is associated with a 13% to 20% prevalence of POCD in patients with AF at long-term follow-up. These results were seen in a patient population with predominant CHADS2 (Congestive heart failure, Hypertension, Age ≥75 years, Diabetes mellitus, previous Stroke/transient ischemic attack) scores of 0 to 1, representing the majority of patients undergoing ablation for AF. The long-term implications of these subtle changes require further study. Copyright © 2013 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.